Coenzyme Q10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ10), also named as ubiquinone or ubidecarenone, exists widely in animals, plants and microorganisms, and is an essential hydrogen carrier in respiratory chain of biological cells. Coenzyme Q10 is an important biochemical medicament, and recently has been widely applied in the treatment of various diseases such as cardiovascular diseases, diabetes, cancers, acute and chronic hepatitis, and Parkinson's Disease. In addition, coenzyme Q10 also exhibits a significant effect on the treatment of scurvy, duodenal ulcer and necrotic periodontitis, as well as on the enhancement of the function and secretion of pancreas. Meanwhile, coenzyme Q10 also has an anti-aging effect, and is widely applied in the fields of cosmetics and health products.
There are mainly three kinds of methods for producing coenzyme Q10, namely, i) extraction from animal or plant tissues, ii) chemical synthesis, and iii) fermentation using microorganisms. In the method of extraction from animal or plant tissues, due to low content of animal coenzyme Q10, complicated chemical components, and the limitation of raw materials and sources, the product cost and price are high, and the industrial production is limited to some extent. Chemical synthesis methods are relatively mature technically, but the products are mixtures of cis-isomers and trans-isomers and have low biological activity, and the production cost is high. Therefore, chemical synthesis methods are limited in industrial production. Fermentation methods using microorganisms have become the most prospective methods for producing coenzyme Q10 for the following reasons: raw materials are cheap and abundant; processes for isolation of products are relatively simple; the products are natural products, without the problems generated by isomers; the products have good biological activity and are capable of being absorbed easily in human bodies; and the production in an industrial scale can be accomplished by using fermentation tanks.
During fermentation using microorganisms, seed incubation is the first step for fermentation production, and the quality of seed liquid plays a key role in fermentation production. Seeds with good quality may shorten the fermentation period, stabilize yield and quality, and enhance utilization of devices. Therefore, seed incubation is essential for the production of coenzyme Q10 by fermentation. Currently, the general processes for producing coenzyme Q10 by fermentation using stock culture are as follows: culture in a slant medium→preparation of stock culture→primary enlargement culture→secondary enlargement culture→tertiary enlargement culture (if necessary)→fermentation. In most of the processes, stock culture are cultured by liquid phase fermentation.
Chinese Patent No. CN101519681, which is incorporated by reference, discloses a method for producing coenzyme Q10 by fermentation, wherein the quality of coenzyme Q10 produced thereby is maintained. In this method, the initial metabolic reaction is modulated in a feedback manner, depending on the synthetic rate and the content of the main side-product (i.e., 5-demethoxy coenzyme Q10) during metabolism of coenzyme Q10-producing bacteria, and has a rate-limiting effect on synthetic metabolism, so as to modulate the accumulation of the product of interest (i.e., coenzyme Q10) in cells in a feedback manner. By optimization of the concentration of the main substrates in the fermentation formulation and by optimized modulation of stirring rate during fermentation, the fermentation level of coenzyme Q10 is greatly enhanced, and the fermentation level of coenzyme Q10 can be enhanced to 3000 u/ml or more; and the determination of the optimized timing of discharging into the fermentation tanks improves time availability for producing coenzyme Q10 in cells, reduces fermentation cost, and greatly reduces the consumption of raw materials for fermentation.